EVO756 / Evommune, Maruho - LARVOL DELTA

EVO756 potently blocks MRGPRX2-mediated mast cell activation as well as MRGPRX2 and IgE-dependent synergistic responses (IMMUNOLOGY 2025) - "We also demonstrate synergism between MRGPRX2-mediated and IgE-dependent primary human mast cell activation, which is inhibited by EVO756. These studies establish EVO756 as a potent inhibitor of MRGPRX2-mediated mast cell activation and therefore, a promising therapeutic for the treatment of mast cell driven diseases.Keywords: Animals Human; Cells Mast Cells/Basophils; Diseases Autoimmunity; Molecules Cytokines; Processes Inflammation"

Late-breaking abstract • Asthma • Atopic Dermatitis • Chronic Spontaneous Urticaria • Dermatitis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Respiratory Diseases • Ulcerative Colitis • Urticaria • GPRC6A

EVO756: A Promising Oral MRGPRX2 Inhibitor Showing Strong Preclinical and Phase 1 Results (FOCIS 2025) - "With promising results from preclinical and Phase 1 studies, EVO756 holds great potential as a treatment for diseases involving mast cells and neuro-inflammation. Further exploration is warranted to unlock its full clinical potential."

P1 data • Preclinical • Atopic Dermatitis • Dermatitis • Immunology • Inflammation

Phase 2b Study of EVO756 in Adults With Moderate to Severe Chronic Spontaneous Urticaria (CSU) (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Evommune, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Study Evaluating the Safety, Tolerability, and Efficacy of EVO756 in Adults With Chronic Inducible Urticaria (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Evommune, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Dermatology • Immunology • Urticaria

Evommune Initiates Phase 2b Trial of MRGPRX2 Antagonist, EVO756, in Adults with Moderate to Severe Chronic Spontaneous Urticaria (PRNewswire) - "Evommune...announced the enrollment of the first patient in a global Phase 2b trial of EVO756, an orally available, highly potent and selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2), in adults with moderate to severe chronic spontaneous urticaria (CSU)....'In addition, we are planning to initiate a separate Phase 2b trial of EVO756, in atopic dermatitis, later this year'....'We look forward to reporting the CSU data in 2026'."

New P2b trial • P2b data • Trial status • Atopic Dermatitis • Chronic Spontaneous Urticaria

A Randomized Dose-ranging Study of EVO756 in Adults With Moderate to Severe Chronic Spontaneous Urticaria (CSU) (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Evommune, Inc.

New P2 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Study Evaluating the Safety, Tolerability, and Efficacy of EVO756 in Adults with Chronic Inducible Urticaria (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Evommune, Inc.

New P2 trial • Dermatology • Immunology • Urticaria

Evommune Initiates Phase 2 Trial of EVO756, an Oral MRGPRX2 Antagonist, in Chronic Inducible Urticaria (PRNewswire) - "Evommune...announced the enrollment of the first patient in a Phase 2 trial of EVO756 in adults with CIndU....The multi-center trial is designed to evaluate the safety and efficacy of EVO756 in approximately 30 patients with either symptomatic dermographism or cold urticaria, the two most common forms of CIndU. Efficacy endpoints include changes from baseline in disease specific provocation thresholds that are used as objective markers to quantify disease severity and response to treatment....'We are also on track to initiate a Phase 2b trial in chronic spontaneous urticaria in the second quarter of 2025'."

New P2b trial • Trial status • Chronic Spontaneous Urticaria

EVO756, a Novel, Small Molecule Antagonist of MRGPRX2, Potently Inhibits Primary Human Mast Cell Activation (FOCIS 2024) - "These findings were further confirmed by quantification of tryptase released in the culture supernatant. Therefore, EVO756, which potently inhibits MRGPRX2 mediated mast cell activation, represents a promising therapeutic for the treatment of mast cell driven diseases such as chronic spontaneous urticaria.."

Immunology • Inflammation • CD63 • LAMP1

Transcriptional profiling of primary human-skin derived mast cell activation by various MRGPRX2 agonists and inhibition with EVO756 (IMMUNOLOGY 2024) - "Furthermore, EVO756 does not affect mast cell viability. Here, we describe, for the first time, the transcriptional landscape of primary human skin-derived mast cells cultured in the presence of several MRGPRX2 agonists and analyze how the mast cell phenotype is altered in response to MRGPRX2 inhibition by EVO756."

Late-breaking abstract • Allergy • Asthma • Atopic Dermatitis • Chronic Spontaneous Urticaria • Dermatitis • Dermatology • Immunology • Pulmonary Disease • Respiratory Diseases • Urticaria • GPRC6A

Evommune Announces Initiation of a Phase 1 Trial of its MRGPRX2 Antagonist for the Treatment of Chronic Spontaneous Urticaria (PRNewswire) - "Evommune, Inc...today announced the initiation of its Phase 1 first-in-human study, evaluating EVO756 in heathy adults and adults with chronic spontaneous urticaria (CSU)...'As a company committed to developing a pipeline of therapeutics to halt the progression of chronic inflammatory diseases, we are excited to dose the first volunteer in our Phase 1 trial of EVO756.'....The Phase 1 study is a randomized, double-blind, placebo-controlled single and multiple ascending dose (SAD and MAD) study in normal healthy adults and an open label study in adults with CSU."

Trial status • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

EVO756 is a novel MRGPRX2 antagonist that potently inhibits human mast cell degranulation in response to multiple agonists – potential treatment for CSU and beyond (ISDS 2023) - "EVO756 potently inhibited MRGPRX2-transfected CHO-cell activation upon stimulation with substance P, ciprofloxacin, compound 48/80, PAMP, or icatibant. We conclude that EVO756 is a potent antagonist of MRGPRX2 activation and can prevent degranulation of human mast cells derived from a variety of origins and different donors, in response to various MRGPRX2 agonists. EVO756 may prove to be an effective treatment for diseases caused by inappropriate mast cell activation, including chronic spontaneous urticaria."

Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • CORT

Evommune Announces Strategic Collaboration with Maruho to Develop and Commercialize MRGPRX2 antagonist EVO756 in Japan (PRNewswire) - "Evommune, Inc...announced that it has entered into a strategic collaboration with Maruho Co., Ltd., to exclusively develop and commercialize EVO756 in Japan. Under the terms of the agreement, Evommune is eligible to receive up to $60 million in upfront and customary milestone payments. In addition, Evommune is eligible to receive meaningful royalties on future sales of EVO756 in Japan....Evommune is currently completing the final stages of non-clinical development and expects to submit an Investigational New Drug (IND) Application for EVO756 to the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2023. The Company plans to initiate clinical programs for various diseases in early 2024, subject to clearance by the FDA."

IND • Licensing / partnership • New trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology